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108 Selected Disorders of the Female Reproductive System

Gary R. Newkirk and Patricia Ann Boken

Pelvic is one of the most vexing problems encountered the patient's efforts to cope with, and her fears about, the by the family physician. The monetary and psychosocial costs cause of pain. are unknown hut are assumed to be high. In the United States Research has shown a high incidence of sexual abuse as• about 40% of all laparoscopies are done for the evaluation sociated with chronic pain.3 Furthermore, current psychiatric and treatment of . I diagnoses, especially depression, and substance abuse corre• late with pelvic pain. Rates of childhood or adult sexual or physical abuse are as high as 4S% in patients presenting with Evaluation of Pelvic Pain chronic pelvic pain.3 Formal psychological consultation may be useful for as• Clinical Presentation sessing the psychiatric contribution to chronic pelvic pain. In Patients with pelvic pain present with a wide variety of com• most instances a psychiatric diagnosis modifies the patient's plaints and physical findings. To better understand the causes perception and significance of pelvic pain and rarely is the of pelvic pain and assist with the initial evaluation, it is help• sole cause of symptoms. ful to distinguish acute pelvic pain from chrouic pelvic pain. Chronic pelvic pain is present for 6 months or more and acute Physical Examination pelvic pain for less than 6 months. Chronic pelvic pain syn• The physical examination includes careful abdominal, mus• drome is characterized by incomplete response to treatment, culoskeletal, and pelvic examination. In addition to the rou• impairment at work or home, signs of depression, and pain tine abdominal examination, the examiner looks for trigger that is worse than would be expected on the basis of the patho• points in the abdominal wall. The abdominal wall has been logic process2 (see Chapter 61). identified as a common source of pain for both acute and chronic forms of pelvic pain.4 The abdominal wall is palpated Diagnosis with the patient's abdominal muscles stretched (supine) and Effective evaluation of pelvic pain begins with a search for relaxed (lmees bent), so trigger points typical of the myofas• organic causes that require immediate therapy. An integrative cial syndrome can be detected. 2 During the pelvic examina• approach that relates psychological. historical, and physical tion the external genitalia are examined for signs of sexually factors from the outset is essential. When taking the history transmitted diseases or trauma. The bimanual examination it is helpful to differentiate acute from chronic pelvic pain be• evaluates the introitus, levator sling, vaginal walls, , cause this distinction refines the differential diagnoses (Ta• , adnexa, septum, and cul-de-sac. The urethra is pal• bles IOS.1 and IOS.2). A detailed history is obtained clarify• pated from within the vagina, as significant pain in this area ing the location, severity, and inciting and relieving factors implies the urethral syndrome related to chlamydial infection. of the pain. Careful menstrual, pregnancy, and sexual histo• The patient is requested to contract and relax the vagina ries are sought. Contraceptive use, previous pelvic problems around the examining fingers to assist in the detection of or surgery, and previous diagnostic and therapeutic efforts are . An attempt is made to re-create the pain on the clarified. The psychosocial history includes clarification of bimanual examination including palpation and movement of prior sexual abuse, personal relationships, and exploration of the cervix. If pressing on the posterior fourchette or bottom

R. B. Taylor et al. (eds.), Family Medicine © Springer Science+Business Media New York 2003 WK. Seleltt'd Disorders ot tht' fern

Tahle 108.1. Causes of Acute Pelvic Pain and Musculoskeletal dysfunction often contributes to the signs Initial Management and symptom~ of chronic pelvic pain and in many cases is the Pelvic infection-antibiotics primary factor.s King et al 6 found that a typical pattern of Pregnancy complications faulty posture, tenned typical pelvic pain (TPP) posture, was Ectopic pregnancy-Iaparoscopy or methotrexate found in 75o/r of patients studied with chronic pelvic pain. The Spontaneous abortion-may need dilation and rurettage posture consists of exaggerated lordotic posture of the lumbar Septit"' abortion-antibiotics, may need dilation and spine, anterior tilt of the pelvis, and kyphosis of the thoracic curettage spine. Referred source~ of pain must also be considered.6.7 Adnexal problems --often require~ laparoscopy Ruptured -may require surgery Diagnostic Studies Intracapsular or f'xtracapsular ovarian hemorrhage-may The initial laboratory evaluation for pelvic pain includes a preg• require surgery nancy test if the patient is of reproductive age, complete blood -specific therapy (see next section) count (CBC), urinalysis, and erythrocyte sedimentation rate Acute degeneration or torsion of a leiomyoma-often (ESR). Vaginal probe ultrasonography can confirm intrauterine requires surgery pregnancies as early as 4 to 5 weeks and can assist in the eval• Nongynecologic causes uation of women with suspected ectopic pregnancy. The pres• Inflammatory bowel disease-specific medical management ence of fluid in the posterior cul-de-sac seen on the ultrasound Urinary tract stone-may require surgical removal, ~can ~uggesb a pathologic process, but this finding has poor antibiotics specificity. Ultrasonography may also he useful for patients who Acute cystitis-antibiotics are difficult to examine because of obesity, are unable to relax, Sexual abuse or whose pain prevents palpation during the bimanual exami• Miscellaneous causes-require specifir medical treatment nation. Unfortunately, abdominal ultrasonography is sometimes Sickle cell disease, porphyria, diabetes, systemic lupus overutilized, as the likelihood of positive findings in a patient erythematosus with completely normal pelvic examination is low and may con• Hf'reditary angioneurotic edema tribute to further unnecessary imaging and heightened physician and paticnt anxiety, For example, ovarian cysts are a common finding on ultrasound scans and may be up to 5 cm in diame• of the vagina reproduces the pain, there is a high likelihood ter: yet they are not the source of pain unless careful bimanual that the pain has a significant psychological or muscu• palpation of thesc cysts duplicates the pain. loskeletal origin. Pain of pelvic organ origin may be noted Diagnostic laparoscopy remains an important tool for eval• ventrally or both dorsally and ventrally but almost never pres• uating pelvic pain. x Laparoscopy is the gold standard for di• ents as dorsal back pain alonc. The cul-de-sac is palpated for agnosing such conditions as pelvic inflammatory disease abnonnalities such as noduier:., which can be found with en• (PID), ectopic pregnancy, and ovarian torsion. The cause of dometriosis. In most instances the cervix is scrcened or cul• chronic pelvic pain in patients under age 30 is most often en• tured for gonorrhea and Chlamydia. dometriosis or chronic PID. Older patients are most likely to have , leiomyomas, endometriosis, or symptoms due to pelvic relaxation. Pelvic adhesions are the only find• Table 108.2. Causes of Chronic and Cyclic Pelvic Pain ing in 10% to 25% of laparoscopies for chronic pelvic pain, Chronic pelvic pain but studies arc still not clear whether adhesions are inciden• Endometriosis tal findings or are the cause of the pain. Another benefit of Chronic Severe pelvic adhesions diagnostic laparoscopy is to offer the patient reassurance. In Adenomyosis one study that followed patients with chronic pelvic pain af• Pelvic congestion syndrome ter laparoscopy had excluded pelvic pathology, 22% were Nongynecologic causes pain-free at their fi week follow-up appointment, and 40% re• Musculoskeletal ported decreased pain.9 Inflammatory bowel disease Other diagnostic studies that may aid in the diagnosis in• Irritable bowel syndrome clude urine cultures, barium enema, intravenous pyelography, Diverticuliti~ Interstitial cystitis and empiric nerve blocks to help confinn the origin of pain Referred pain (e.g., symptomatic adenomyosis). Psychological Cyclic pelvic pain Management Mittelschmerz Primary The patient with acute, severe pelvic pain and deteriorating Secondary dysmenorrhea clinical condition often requires abdominal exploration. In Adenomyo~is most other instances, a careful history and physical examina• tion indicate the most likely nonsurgical causes of acute pelvic Pedunculdted submucous myoma pain. Table 108.1 outlines initial management steps for the Prf>menstrual tension :.yndrome various causes of acute pelvic pain. 910 Gary R. Newkirk and Patricia Ann Boken

Narcotics can be used with acute pelvic pain on a selective early in the investigation of CPP sufferers, such as clarifying basis, when the diagnosis is assured, and for a short time. Nar• sexual or physical abuse, may avoid extensive medical eval• cotics should not be used for chronic pelvic pain. Nonsteroidal uations and onnecessary sorgical procedures (see Chapter 27). antiinflammatory drugs (NSAIDs) are the best choice for Appropriate postore along with good physical conditioning, long-term causes of pelvic pain. Antidepressants help with the nutrition, and regular exercise may prevent the muscu• management of chronic pelvic pain regardless of whether loskeletal origins of pelvic pain. symptoms of classic depression are identified, and they can be ttied on an empitic basis. Low-dose amittiptyline (25 mg) Family and Community Issues was significantly more effective than placebo in reducing such pain. to The multiple causes of pelvic pain make its treatment and di• Honnone treatment with oral contraceptives, Depo-Provera, agnoses challenging. Family physicians are uniquely qualified and gonadotropin-releasing honnone (GnRH) analogues may to care for patients with pelvic pain by virtue of their psy• be helpful in suppressing ovarian function to treat conditions chosocial evaluation skills, long-term management potential, such as endometriosis, adenomyosis, fibroids, dysmenorrhea, and general ability to coordinate care from various consult• and ovarian cysts. Definitive treatment with antibiotics and ants. Education of the community about sexual abuse, STDs, the occasional need to drain pelvic abscesses surgically are PID, endometriosis, depression, and other factors associated the main strategies for managing PID. with pelvic pain can be offered by the family physician. Several studies have reported the importance of a multi• disciplinary management for treatment of chronic pelvic pain (CPP). Sexual and marital counseling, family therapy, and be• Endometriosis: Diagnosis and Therapy havior modification therapy are interventions to be consid• The presence of tissue that is biologically and morphologi• ered. Regular office visits should he scheduled to decrease cally similar to normal in locations beyond the the patient's need to justify visits by experiencing more pain. endometrial cavity is termed endometriosis. 13 Endometriosis The frequency of these visits can he gradually tapered as the affects approximately 7% to 10% of premenopausal women. I4 patient improves. Realistic goals must be established early re• The prevalence in the general population may be underesti• garding the management of CPP.!! Adapting and coping with mated, as not all endometrial lesions exhibit classic morpho• CPP is considered the therapeutic goal, with complete reso• logic fmdings at Iaparoscopy.IS Endometriosis is found in lution of symptoms unlikely. 30% to 60% of women who present for evalua• Adjunctive treatment includes nerve blocks and nerve in• tion. I6 Sixty to seventy percent of women with endometrio• terruption surgery. Paracervical blocks may have a diagnos• sis are nulliparous, and most have a family history.n The tic and therapeutic value, as a response to this trial of anal• pathophysiology of endomettiosis remains incompletely char• gesia strongly implies a uterine source for the pelvic pain. acterized and poorly understood. The most widely accepted ex• 4 Fascial injections were advocated by Ung and Slocomb for planation for endometriosis focuses on the concept of retro• myofascial origins of pelvic pain. Laser uterine nerve abla• grade flow of menstroa1 fluid back through the fallopian tubes tion therapy has had mixed results when used to manage uter• with implantation of viable endomettial tissue in the free ine sources of pain. Patients often adamantly demand a hys• pelvis. I8 This explanation contrasts with the coelomic meta• terectomy, especially when the search for the etiology of CPP plasia theory, which argues that undifferentiated coelomic ep• becomes nonproductive. Interestingly, in one study looking ithelial cells remain donnant on the peritoneal surface until the at the outcome of women undergoing hysterectomy with CPP, produce honnones sufficient to stimulate this ectopic I2 78% showed significant improvement. tissue. 14 Despite the controversies surrounding pathophysiol• Other, less traditional therapies for CPP include physical ogy, endometriosis remains one of the most common gyneco• therapy for musculoskeletal dysfunction, stressing manage• logic diseases in women during their reproductive years. ment through lifelong attention to posture, strength, and flex• ibility; transcutaneous electrical nerve stimulation (TENS) for musculoskeletal abdominal wall or back pain; acupuncture; Clinical Presentation and relaxation and biofeedback. Endomettiosis is rarely life-threatening but frequently be• comes life-altering. Patients with endometriosis present a wide range of clinical symptoms, and frequently there is poor cor• Prevention relation between these symptoms and the extent of endome• Early management of the symptoms of acute pelvic pain and ttial implants within the pelvis. Dysmenorrhea (50%), infer• identifying the source decreases the possibility of symptoms tility (25-50%), pelvic pain and (20%), and becoming chronic. In the patient who is sexually active, coun• menstrual irregularities (12-14%) are the most common corn• seling regarding sexually transntitted diseases (STDs) and plaints. I9 Pain can be diffuse or localized to the organs in• their prevention is always prudent. The use of estrogen in volved. Other, less common symptoms include low back pain, postmenopausal women may be helpful for preventing pelvic dysuria, hematuria, and diarrhea, which classically occur be• pain due to vaginismus. The use of NSAIDs for 3 days prior fore or during menses. Despite classic descriptions of the dis• to and during menses is beneficial in prevent• ease, endometriosis may present with some, none, or all of ing pelvic pain caused by dysmenorrhea. A thorough history these symptoms, which mayor may not correlate with the men- 108. Selected Disorders of the Female Repoductive System 911 strual cycle. Textbooks describe the typical endometriosis pa• prompt many clinicians to include pelvic ultrasonography in tient as in her late twenties or early thirties, Caucasian, and the workup of endometriosis. frequently nulliparous. In reality, endometriosis occurs with A cell surface antigen, CA-125, is found on derivatives of all races from early adolescence to the perimenopausal period. coelomic epithelium including endometrial tissue. Despite the Endometriosis should also be considered in women initially correlation of CA-125 levels with both the degree of en• presenting for evaluation of infertility.20 How endometriosis dometriosis and the response to therapy, the sensitivity of this contributes to infertility is not known, and likely more than assay is too low for it to be used as a screening test. The meas• one mechanism is involved. Explanations include altered urement of peritoneal fluid levels appears to be better for de• anatomy, ovulatory dysfunction, hormonal abnormalities, au• tecting minimal and moderate disease. 24 It may be beneficial toimmunity, toxic pelvic factors, altered sexual functioning, to utilize this test when evaluating ovarian cystS.25 Develop• and increased spontaneous abortions,16,19 Even though it ap• ing a serum endometrial antibody assay continues to be in• pears that the number of pelvic implants does not correlate vestigated, with its sensitivity and specificity greater than 0.9 well with the severity of dysmenorrhea and dyspareunia, the in detecting endometriosis.25 probability of successful conception appears to be inversely related to the severity of the disease. 21 Recent prospective Management26,27 controlled trials suggest that minimal to mild endometriosis Treatment for endometriosis is preceded by careful confirma• is not associated with reduced fecundity. 22 tion and stagiog with Iaparoscopy or laparotomy. Factors to con• sider prior to treatment include the patient's age and desire for Diagnosis fertility, the severity of symptoms, and the extent, location, and Patients presenting with pelvic pain, dyspareunia, dysmenor• severity of the disease. Even though there is no universally ef• rhea, abnormal bleeding, or infertility should prompt the cli• fective cure for this disorder, treatment options do exist that can nician to consider endometriosis as a diagnosis. Physical fmd• provide relief of symptoms. The wide variety of treatments for ings include uterosacral nodularity, retroversion of the uterus, endometriosis betray its poorly defined etiology and path(}• limited pelvic mobility, adnexal masses, and diffuse or focal physiology. Treatment includes expectant management, con• tenderness. Unfortunately, neither the history nor the physi• servative surgical therapy, medical therapy, extensive surgery cal examination confinns the diagnosis of endometriosis. The with castration., and superovulation therapies for infertility, such diagnosis of endometriosis requires direct visual and histo• as in vitro fertilization or gamete intrafallopian tube transfer logic conflrmation obtained during laparoscopy or laparo• (GIFf). With more advanced endometriosis, there is a greater tomy. A unifonn system of classification based on the pres• likelihood that surgical intervention will be required to treat the ence, location, and quality of adhesions, , and disease successfully. Surgical removal of both ovaries invari• tubal distortion has been fonnulated by the American Fertil• ably induces remission of the disease but should be reserved for ity Society (AFS). The AFS classifies endometriosis as min• women with advanced endometriosis who are over 35 years of imal, mild, moderate, and severe (stages I to IV, respec• age and do not intend to become pregnant. tively).23 During laparoscopy or laparotomy, endometriosis Expectant management, or watchful waiting, may be a rea• may appear as classic brown lesions that may be focal (e.g., sonable management strategy for the younger woman who de• ovarian) or diffuse (e.g., peritoneal). Reddish blue nodules on sires pregnancy and has mildly symptomatic endometriosis. the peritoneum, uterine ligaments, or pelvic viscera are a com• Efforts can then be spent identifying and correcting any other mon finding as well. Focal scarring or retraction of the peri• infertility factors as necessary (see Evaluation of the Infertile toneum, diffuse adhesions, and distortion of uterine, ovarian, Couple, below). This approach has been shown to produce and tubal anatomy can be seen. Ovarian implants may result pregnancy rates as high as those achieved with medical ther• in the fonnation of an . These ovarian masses, apy or conservative surgery (50%).28 or "chocolate cysts," can explain the fmding of a tender ad• Conservative surgery for endometriosis entails either la• nexal mass on pelvic examination. The presence of en• paroscopy or laparotomy and is indicated (1) for confinna• dometriomas is confmned during laparotomy and may con• tion of diagnosis; (2) if fertility is desired, to determine tubal stitute the initial finding for endometriosis. Extrapelvic (e.g., occlusion or peritubal, pelvic, or ovarian adhesions; (3) for , vagina) or pelvic endometriosis should be considered aspiration of chocolate ovarian cysts; and (4) for evaluation with any mass or lesion that becomes painful in a cyclic fash• of pelvic pain unrelieved by medical therapy.16 The initial ion with menses. treatment at the time of diagnostic laparoscopy can often be Computed tomography (CT) and magnetic resonance im• accomplished with electrocoagulation or laser ablation of im• aging (MRI) can provide presumptive evidence of endo• plants through the laparoscope. Partial ovarian resection for metriosis but are rarely justified for the initial workup. These endometriomas and lysis of adhesions are accomplished as expensive imaging studies are not diagnostic, as there is no necessary. Definitive surgery includes total hysterectomy and characteristic appearance or location for endometriosis im• bilateral salpingo-oophorectomy and is indicated in women plants. Pelvic ultrasonography is not diagnostic either but can who do not desire pregnancy and for whom all previous med• be helpful in detecting and characterizing pelvic pathology if ical and conservative surgical efforts have failed. the pelvic examination is limited owing to tenderness or obe• Medical management of endometriosis includes the use of sity. Its common availability, lower cost, safety during preg• danazol, progestins, oral contraceptives, and GnRH agonists. nancy, and nonradiographic nature are general features that The goal of honnonal therapy is to control symptoms or im- 912 Gary R. Newkirk and Patricia Ann Boken prove fertility, or both. Most medical regimens involve treat• are consistent with endometriosis, empiric medical therapy ment for at least 6 months, allowing for adequate regression may be tried prior to defmitive surgical diagnosis. In a of implants. prospective study it was concluded that after failure of initial Endometriotic implants behave like nonnal endometrial tis• treatment with oral contraceptives and NSAIDs, empiric ther• sue and are supported by ovarian hormones.29 The effective• apy with 3 months of a GnRH agonist is appropriate.3l ness of hormonal management takes advantage of the bio• Infertility associated with endometriosis has now been logic response of endometriotic tissue to alterations of the treated with advanced reproductive techniques including ad• hormonal environment. In either a hypoestrogenic or a hy• ministration of hyperstimulation gonadotropins, in vitro fer• perandrogenic environment, endometriotic implants become tilization, and GIFT techniques,32-34 The fantily physician as• atrophic. Danazol (Danocrine), for instance, induces a hyper• sumes a critical role in managing endometriosis by arranging androgenic state, and GnRH agonists produce a hypoestro• for appropriate consultation, monitoring medical treatment genic state. Both agents induce regression of endometriotic protocols, and providing long-term emotional support to pa• implants. Progesterone therapy such as medroxyprogesterone tients and families troubled by this chronic condition. acetate (Cycrin, Provera) induces decidual or atrophic changes in endometriotic implants. Finally, administration of combined estrogen-progestogen contraceptives (pseudopreg• Prevention nancy regimen) produce an acyclic hormonal environment At present there are no known effective interventions to pre• similar to that of pregnancy, which causes endometriotic im• vent endometriosis from developing in a given patient. A pos• plants to atrophy. 30 Table 108.3 summarizes various treatment itive family history and deferring childbearing lead to a higher strategies, the common drugs used for therapy, and their po• likelihood for the development of endometriosis. Endo• tential side effects. Severe endometriosis and infertility often metriosis usually recurs despite medical or conservative sur• require an organized treatment plan combining surgical and gical treatment.l7 Long-term hormonal therapy without sur• prolonged medical treatment. In a woman whose symptoms gery can help prevent progression in some patients with severe

Table 108.3. Major Treatment Modalities for Endometriosis Hormonal Route of Typical Method effect Drug administration daily dose Problems Bilateral Hypoestrogenic NA laparotomy NA Permanent sterility, oophorectomy bone loss, (often with menopausal hysterectomy) symptoms Laser or electro- NA NA laparoscopy or NA Surgical risks; ? fulguration laparotomy benefit for ablation of severe disease, endometrial recurrence implants GnRH agonist Hypoestrogenic Nafarelin Nasal 0.4-0.8 mg bid Bone loss, hot (Synarel) X 6 months flashes, decreased libido, leuprorelin 1M 3.75 mg per month (Lupron) for 6 months Goserelin SC 3.6 mg per month (Zoladex) for 6 months Androgenic Hyperandrogenic Danazol Oral 400--800 mg Androgenic side agonist (Danocrine) effects, weight gain, oily skin, deep voice High Hyperprogestational Medroxyproges- Oral 30-60 mg Mood changes, progesterone (relative low terone acetate bloating, estrogen) (Provera), breakthrough norethindrone bleeding acetate (Aygestin) Continuous oral Combined estrogenic Birth control pills Oral e.g., 0.035 Oral contraceptive contraceptives and progestational (many types) mg ethinyl• side effects: (pseudo• estradiol/l mg mood changes, pregnancy) norethindrone weight gain, or cyclic 11-4 per day) bloating, hypertension NA = not available; SC = subcutaneous. 108. Selected Di::.orders of tilt:' Fem,lle Reporluctive System 913 symptoms. Only definitive surgery such as abdominal hys• Tahlc 108.4. Male and Factors terectomy with bilateral salpingo-oophorectomy, combined Male factors (40% of couples) with resection of all endometrial implants, yields the highest f)i~orrlers of spermatogenesis likelihood for resolution of symptoms. The laparoscopic find• Obstrur:tion of efferent ducts ing of minimal endometrial disease in a woman not desiring Disorders of sperm motility pregnancy can frequently be managed with cyclic birth con• trol pills to lessen further seeding. More advanced disease Female factors (45°/,) of couples} usually requires 6 months of danazol or medroxyprogesterone Pelvic origin (30-50% of female causes) rubal disorders acetate followed by cyclic birth control pills. 2() Uterine disorders Endometriosis Family and Community Issues Ovulatory origin (40% of female causes) Fndocrine (adrenal, thyroid, pituitary) disorder Education regarding endometriosis ideally begins during early Ovarian: defects adolescence as part of comprehensive health education. Cervical origin (10% of female causes) Women should be encouraged to seek medical help for the Mucous problems symptoms of endometriosis. For many women endometriosis Infectious problems becomes a chronic afiliction that requires ongoing education. Combined factors (15-30% of couples) treatment, and compassion. If the patient requests, the physi• Unidentifiable factors (15% of couples) cian should meet with other members of the family to offer information and address questions or concerns. Patients and families may benefit from contacting the Endometriosis As• Initial Fertility Workup sociation to obtain educational materials and information re• A timely and cost-effective approach to evaluating the infer• garding support groups that deal with the impact of thi" tile couple requires initial evaluation of both the male and fe• chronic condition.35 Women with documented endometriosis male factors for infertility. Table 108.5 summarizes an or• who desire pregnancy should be counseled regarding its re• ganized approach to the fertility workup.39-42 Both partners lation to infertility, so these desires and the timing of child• are scheduled for extended examination times. Ample time is bearing can be discussed. Effectively managing patient~ with afforded to explain the need and methods for the various ini• endometriosis challenges the family physician to remain an tial tests and data collection including (1) semen analysis, (2) informed patient advocate, as comprehensive care frequently documentation of , (3) postcoital test, and (4) eval• involves referral and familiarity with long-term treatment uation of tubal patency. The exact sequence in which a physi• modalities not routinely used by family physicians.-'6 cian evaluates a couple's infertility varies based on historical and physical findings ascertained during the initial visit. Evaluation of the Infertile Couple A semen sample is analyzed within 2 hours of ejaculation after 48 hours of ejaculatory abstinence. Evaluation should be Infertility is generally diagnosed when pregnancy has not oc• by persons experienced with fertility semen analysis. If an ab• curred in a couple trying to conceive after 1 year of unpro• normality is found on this initial assessment, two additional tected intercourse. It is estimated that nearly 15% of couples semen analyses arc performed 2 weeks apart. If the abnor• in the United States are infertile.~7 The infertility risk dou• mality persists, urologic consultation is appropriate.4 :1 bles for women of ages 35 to 44 compared to women of ages Assessing ovulation can be accomplished by one or more 30 to 34; consequently, about one third of women older than methods: (I) (BBT) assessment; (2) 35 who desire pregnancy experience infertility.JH timed serum progesterone levels; (3) urinary luteinizing hor• Couples are seeking professional help for infertility on a in• mone (LH) screening; and (4) endometrial biopsy. The creasing basis. and family physicians are in an ideal position method of recording BBT data is explained during the initial to begin this evaluation. Their familiarity with partner's fam• visit. Serum progesterone levels are measured 7 days after es• ily, medical, and physical histories allow the assessment to be• timated ovulation. Values consistent with ovulation vary with gin with both partners, which contributes to the cost-effective• each laboratory, but generally values of more than 15 ng/mL ness of the family physician's infertility evaluation. The major arc consistent with nonnal ovulatory function and levels un• goals when evaluating the infertile couple include (I) identify• der 5 ng/mL imply . ing and correcting causes of infertility, (2) providing accurate Endometrial biopsy. in addition to histologically detecting information for the couple, (3) providing emotional support ovulation, provides timing of the progestational effect with during and after the evaluation process, and (4) providing coun• the day of the cycle and can provide information regarding seling regarding alternatives should pregnancy be unlikely or ovulation and luteal phase defects. Endometrial sampling is impossible.J9 This discussion presents the initial workup of the easily accomplished using small aspiration catheters (pipelle, infertile couple, which is sufficient to allow diagnosis in ap• Z-sampler) at as close to 7 days after presumed ovulation as proximately 60% of couples seeking help.4() possible (roughly, day 22 of a 28-day cycle). There are various estimates regarding the causes of infer• Postcoital testing requires evaluation of the spel111-mucus tility. Table 108.4 summarizes the experience for infertile cou• interaction. The couple is instructed to have intercourse fol• ples in the United States.1Y-41 lowing 48 hours of abstinence. Pelvic examination is per- 914 Gary R. Newkirk and Patricia Ann Boken

Table 108.5. Evaluation Plan for the Infertile Couple or laparotomy. The frequency of these visits also facilitates Initial visit (extended visit time for both partners) emotional support and encouragement for the couple. Complete medical, family, drug and sexual history RESOLVE (5 Water Street, Arlington, MA 02174), a national Laboratory studies nonprofit infertility organization, has chapters throughout the Sexually transmitted disease cultures (especially Chlamydia, United States and is an excellent resource for support and Ureaplasma urealyticum, Neisseria gonorrhoeae) counseling groUpS.42 Assess need for HIV screening Consider eBe, FBS, VDRL, urinalysis Men: semen analysis Further Evaluation Women Hysterosalpingography (HSP) is a safe, high-yield procedure Papanicolaou screening when performed during the early proliferative phase of the KOH and wet mount cycle. During HSP a special catheter is passed through the Focused studies vagina into the endocervical canal through which contrast Thyroid history?-thyroid function tests Galactorrhea?-prolactin levels medium is injected and fluoroscopically followed through the Abnormal pelvic examination?-ultrasonography, endometrial and lumen. An undiagnosed pelvic laparoscopy mass or PID contraindicates this procedure, as does an iodine History PID?-hysterosalpingography or radiocontrast dye allergy. HSP can be performed during Endometriosis likely?-Iaparoscopy laparoscopic surgery as well. The appearance of uterine de• History sexual dysfunction?--education" counseling fects on HSP implicates a uterine cause of infertility, which Ovulatory monitoring (BBT, urinary LH) include post-diethylstilbestrol (DES) uterine abnormalities Education Alcohol, drugs, hot tubs, sexual practices/frequency, (T-shaped, hypoplastic cavity), intrauterine synechiae (Ash• douching, lubricants erman syndrome), submucous or large intramural myomas, Arrange for postcoital sample analysis with next visit congenital anomalies, and leiomyomas. Second visit (midcyclelovulatory as predicted by BBT and/or Further evaluation of pelvic factors for infertility requires urinary LH testing) laparoscopy. Laparoscopy is indicated if HSP is contraindi• Review laboratory studies, semen analysis, ovulatory cated or abnormal and is also performed if historical (e.g., monitoring data to date PID, endometriosis) or physical (e.g., adhesions, tube/ovar• Analyze postcoital sample ian abnormality) findings implicate a pelvic cause. Women Consider and discuss need for endometrial biopsy with endometriosis are twice as likely to be infertile as women Arrange for hysterosalpingography during (days 7-9); if laparoscopy deemed necessary, HSP often without this condition. Endometriosis is confirmed and staged accomplished during laparoscopy by laparoscopy. Treatment for endometriosis was discussed Third visit (midluteal phase of cycle, 7-9 days postovulation) earlier in this chapter. Finally, laparoscopy is indicated if no Review studies to date other significant cause of infertility is identified. Perform endometrial sampling Ovulatory causes of infertility include adrenal and thyroid Consider progesterone and prolactin levels if not already done disorders. Fasting blood glucose, thyroid function, follicle• Consider HSP or laparotomy; referral often appropriate at stimulating hormone (FSH), luteinizing hormone (LH), and this time prolactin levels assist the evaluation of endocrinologic factors eBe = complete blood counts; FBS = fasting blood sugar; for infertility. Drug-related infertility must also be considered, LH = luteinizing hormone; HSP = hysterosalpingography; as a number of medications contribute to disruption of thy• BBT = basal body temperature; HIV = human immunodefi• roid. adrenal, or ovarian functioning in women and thyroid or ciency virus; PID = pelvic inflammatory disease. adrenal functioning in men (e.g., antihypertensive drugs, ma• jor tranquilizers, steroids). Therapy for ovulatory factors is formed and aspirated cervical mucus is examined within 2 to directed toward the underlying disorder, including thyroid re• 8 hours of intercourse. Intercourse should occur within 24 to placement for hypothyroidism, bromocriptine for hyperpro• 48 hours of presumed ovulation as determined by methods lactinemia (with pituitary macroadenoma ruled out), or outlined above. The postcoital mucus is examined by experi• clomiphene to induce ovulation. enced individuals for quantity, clarity, pH, spinnbarkeit (abil• Cervical factors for infertility are assessed initially by the ity of cervical mucus to stretch), and the number, forms, and postcoital test. The finding of leukocytes suggests , motility of sperm. Generally, finding 5 to 10 sperm with lin• and cultures for gonorrhea, Ureaplasma urealyticum, and ear motility per high-power field in clear, acellular mucus Chlamydia are useful for directing treatment. Finding non• with more than 8 em spinnbarkeit excludes cervical factors motile or nonprogressively motile sperm with a "shaking" pat• as a major cause of infertility. tern suggests sperm antibodies. Miscalculation of ovulation During a subsequent office visit, results of the initial lab• timing is suggested by poor-quality cervical mucus, which is oratory studies, cultures, and semen analysis are discussed. abnormally thick, cloudy, and demonstrates poor spinnbarkeit. The postcoital sample can be obtained, and an appointment A repeat postcoital test is necessary if ovulatory timing is in for the endometrial biopsy, luteal progesterone, and prolactin question. levels scheduled. The results of these studies are carefully re• Despite comprehensive evaluation 5% to 10% of couples viewed during the third visit, at which time a decision is made have no identifiable cause for their infertility. Often referral to pursue hysterosalpingography, laparoscopy, hysteroscopy, to infertility centers for consideration of assisted reproductive 108. Selected Disorders of the Female Repoductive System 915 technologies (ARTs) is necessary (e.g., in vitro fertilization, In the original studies, patients with TSS usually had a source GIFT) and appropriate. Attitudes regarding adoption and as• of staphylococcal infection. More recent reports have char• sisted reproductive technologies should be explored. acterized a streptococcal toxic shock-like syndrome caused Often individual or joint guilt regarding infertility can be by toxins elaborated by group A streptococci. 53,54 Both have underestimated. Family physicians are in an ideal position to in common the presence of bacteria-related toxins that appear utilize established trust and comfort with their patients to ex• to initiate the serious multiorgan syndrome characteristic of plore potential past history and guilt issues that might relate these disorders. Toxic shock syndrome toxin-l (TSST-l) has to infertility. Emotional support remains a part of every visit.44 been identified as one of the significant staphylococcal me• diators of pathogenicity in TSS," although TSS can occur in the absence of TSST-I. Endotoxin from co-infecting gram• Toxic Shock Syndrome negative or streptococcal bacteria has also been implicated in TSS.56 Staphylococcal toxins may interact synergistically In 1978 an acute, febrile, exanthematous illness associated with these endotoxins. TSST-l enhances the release ofa wide with multisystem organ failure became known as the toxic variety of endogenous mediators produced by the host, which shock syndrome (fSS).4S There are currently no definitive partly explains the multiorgan dysfunction characteristic of tests Of specific serologic markers for diagnosing TSS. The this syndrome. Finally, the correlation of TSS with vaginal diagnosis requires the presence of the six clinical criteria, out• materials such as , barrier sponges, or the diaphragm lined in Table 108.6.46•47 TSS should be suspected in all pa• strongly implies an as yet uncharacterized relation between tients who present with flu-like symptoms, rash, and other• foreign materials and the induction and maintenance of this wise unexplained hypotension. condition. TSS apparently results from multiple, cumulative Early reports indicate that more than 90% of the reported effects of primary and secondary mediators initiated by the TSS cases involved menstruating females.48 Because of the continued growth of certain bacteria. high correlation of TSS with menstruation and use, the perception of TSS as strictly a "tampon disease" persists. Clinical Presentation More recent data reveal that only half of the reported cases Toxic shock syndrome presents with a broad spectrum of clin• were female, and many of these cases were not associated with menstruation.49 Most cases of tampon-related TSS oc• ical findings ranging from relatively mild symptomatology to a rapidly fatal illness.56,57 Mortality is about 3%. Patients may curred during the teenage years; 97% of reported patients were white, and 42% were adolescents. 50 Physicians must recognize progress from onset of symptoms to overt multisystem fail• that TSS can occur in nonmenstruating women, men, and chil• ure within 48 hours. Hypotension and poor tissue perfusion, with nonhydrostatic leakage of fluid from the intravascular to dren of all ages. Nonmenstrual cases of TSS occur in males the interstitial space, accounts for a portion of the multisys• and females equally with various sites and types of infection, tem organ failure (renal, hepatic, central nervous system, including surgical wounds, burns, abscesses, sinus infections, bronchopneumonia, influenza A, tracheitis, empyema, septic hematologic). Fatal complications include refractory shock, abortion, intravenous drug injections, pilonidal abscess, nasal renal failure, arrhythmias, intravascular coagulopathy, and respiratory distress syndrome. The initial fever, rash, and packing, insect or human bites, diaphragm use, and even ear malaise of TSS may mimic a common syndrome early piercing. Interestingly, menstruation-related TSS affects Cau• viral casians almost excJusively, whereas non-menstruation• in the disease process. These symptoms typically progress rapidly to include high fever (104°P), pharyngitis, conjunc• related fonns affect the races proportionate to the racial/sex• tivitis, diarrhea, vomiting, myalgia, and scarlet fever-like ual mix of the population.51 ,52 rash. Within a matter of hours orthostatic dizziness, fainting, or overt hypotension may occur; these first symptoms clearly Pathogenesis set this syndrome apart from benign infectious processes. The The expression of TSS depends on the interaction of several rash of TSS is usually a prominent finding and typically ap• bacterial and host factors that are incompletely understood. pears as a diffuse scarlatinifonn exanthem beginning on the trunk and spreading to the arms and legs with flexural ac• centuation. Some clinicians have described this rash as hav• Table 108.6. Toxic Shock Syndrome, Criteria for Diagnosis ing a "sunburn" appearance that blanches with pressure. Confirmed diagnosis requires that all six criteria be met: "Strawberry tongue," as seen with scarlet fever, is a common 1. Acute fever finding. Erythema of the mucous membranes and intense con• 2. Scarlatiniform rash junctival hyperemia without purulence are characteristic. 3. Desquamation of palms and soles 1-2 weeks after illness Generalized nonpitting edema accompanies the rash in many onset cases. Desquamation of the hands and feet is commonly seen 4. Hypotension 5. Clinical or laboratory evidence of involvement of at least within 10 to 21 days after presentation. Reversible patchy three organ systems: hematologic, gastrointestinal, neuro• alopecia and shedding of fingernails has been described as logic, cardiovascular, hepatic, renal, muscular well.58 6. Other causes excluded (e.g., sepsis, measles, drug or toxic Toxic shock syndrome is rare in children, but when it does ingestion) appear the clinical features of the illness do not differ appre• Source: Data from Todd and Fishaut45 and Tofte and Wi II iams. 46 ciably from those described in adults. There does seem to be a 916 Gary R. Newkirk and Patricia Ann Boken

higher likelihood of respiratory involvement in children. 55 The 2. Nolan TE, Elkins TE. Chronic pelvic pain: differentiating differential diagnosis ofTSS in children includes Kawasaki dis• anatomic from functional causes. Postgrad Med 1993;94: 125-8. ease, staphylococcal scalded skin syndrome, scarlet fever, 3. Toomey TC, Hernandez JT, Gittlelman DF, Hulka JF. Rela• tionship of sexual and physical abuse to pain and psychological Rocky Mountain spotted fever, leptospirosis, erythema multi• assessment variables in chronic pelvic pain. Pain 1993;94: forme, Stevens-Johnson syndrome, and measles. 125-ll. Common laboratory findinga of TSS reflect widespread or• 4. Ling FW, Slocumb JC. Use of trigger point injections in chronic gan involvement: sterile pyuria; normocytic anemia; leuko• pelvic pain. Obstet Gynecol Clin North Am 1993;20:809-15. cytosis with left shift; prolongation of the prothrombin and 5. King Baker P. Musculoskeletal origins of chronic pelvic pain. partial thromboplastin times; an increase in serum bilirubin, Dbstet Gynecol Clin North Am 1993;20:719-40. 6. King PM, Myers LA, Ling FW, et al. Musculoskeletal factors creatinine, and creatine kinase; hyponatremia; hypokalemia; in chronic pelvic pain. J Psych Obstet GynaecoI1991;12:87-98. and metabolic acidosis. 59 7. Basu HK. Major common problems: pelvic pain. Br J Hosp Med 1981;26:15()...8. 8. Vercellini P, Fedele L, Arcaini L, et al. Laparoscopy in the diM Management agnoses of chronic pelvic pain in adolescent women. J Reprod Hospitalization is necessary for all patients with presumed TSS, Med 1989;34:827-32. as the illness may progress from mild to life-threatening within 9. Baker PN, Symonds EM. The resolution of chronic pelvic pain. a matter of hours. Supportive measures tailored to the patient's Am J Dbstet GynecoI1992;166:835-9. symptoms are the mainstay of therapy.60 A search is made for 10. McQuay HJ, Carroll D, Glynn CJ. Low dose amitriptyline in the treatment of chronic pain. Anesthesia 1992;47:646-52. the potential source of the staphylococcal or streptococcal toxin, 11. Parsons L, Stovall T. Surgical management of chronic pelvic and cultures of any suspected source are obtained. Removal of pain. Obstet Gynecol Clin North Am 1993;20:765-78. vaginal tampons, pads, sponges, or diaphragms is paramount. 12. Stovall TG, Ling FW, Crawford DA. Hysterectomy for chronic Recent surgical wounds are explored even if they appear not pelvic pain of preswned uterine etiology. Obstet Gynecol 1990; to be inflamed or infected. AU presumed sources of toxin must 75:676-81. be thoroughly drained aod irrigated. 13. Sampson JA. Perforating hemorrhagic (chocolate) cysts of the , their importance and especially their relation to pelvic Prospective management includes administration of large adenomas of the endometrial type. Arch Surg 1921;3:245-323. volumes of colloid and crystalloid fluids with glucose (10-20 14. Saltiel E, Garabedian-Ruffalo SM. Pharmacologic management mlJkg) over the first hour to reestablish vascular volume. Pa• of endometriosis. Clin Pharm 1991;10:51&-30. tients may require 5 to IO L of fluid during the first 24 hours 15. Rawsn 1M. Prevalence of endometriosis in asymptomatic to maintain tissue perfusion and urinary output Swan-Ganz women. J Reprod Med 1991;36:513-5. catheterization is required for severe cases. After specimens for 16. Dawood MY. Endometriosis. In: Gold JJ, JOsllnovich m, eds. Gy• culture are obtained, aotistaphylococcal antibiotics (e.g., me• necologic endocrinology. New York: Plenum, 1987;387-404. 17. Moghissi KS. Office management of endometriosis. In: thicillin, oxacillin, nafcillin, first-generation cephalospurin, or Stenchever MA, ed. Office gynecology. St. Louis: Mosby-Year vancomycin) are given intravenously until oral fluids can be Book, 1992;413-29. tolerated. Antibiotics are continued for at least 10 days. Steroid 18. National Center for Health Statistics, McCarthey E. Inpatient therapy (e.g., methylprednisolone 10-30 mglkg/day) may be utilization of short-stay hospitals by diagnosis: United States, given to patients with severe unresponsive shock. Intravenous 1980. Hyattsville, MD: National Center for Health Statistics, immune globulin may be also given to patients who are not im• 1982. DHSS Publ. no. (PHS) 83-1735. (Vital and health statis• tics; series 13: Data from the National Health Survey, no. 74.) proving, although the effectiveness of this therapy has not been 19. Hurst BS, Rock JA. Endometriosis: pathophysiology, diagnosis, proved. and treatment. Obstet Gynecol Surv 1989;44:297-304. Signs of adult respiratory distress syndrome (ARDS) often 20. Endometriosis and infertility. In: SperoffL, Glass RH, Kase NG, develop on the second Of third day of treatment with severe eds. Clinical gynecology, endocrinology, and infertility, 4th ed. TSS. Intubation with continuous positive airway pressure may Baltimore: Williams & Wilkins, 1989;547-63. be required; generally, fluids are not restricted. Acute renal 21. Dmowski WP. Endometriosis. In: Glass RH, ed. Office gyne• cology. Baltimore: Williams & Wilkins; 1987;317-36. failure may require dialysis. 22. Berube S, Marcoux S. Langeuiun M, Maheux R. Fecundity of milder. Recurrences of TSS are common but generally Fe• infertile women with minimal or mild endometriosis and women male patients who experience TSS are advised to avoid the use with unexplained infertility. Canadian Collaborative Group of of vaginal devices (tampons, sponges, diaphragms). Prophy• Endometriosis. Ferti1 SteriI1998;69:1034-41. lactic antistaphylococcal oral antibiotics at the time of menses 23. American College of Obstetricians and Gynecologists. Man• have been recommended for patients experiencing TSS asso• agement of endometriosis. Technical bulletin no. 85. Washing• ciated with menses. 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